3430-18-0

Off-white to beige crystalline powder

General procedure for the synthesis of 2,5-dibromo-3-methylpyridine (49) from 2-amino-3-methyl-5-bromopyridine (48, 69 g, 0.37 mol): the raw material was suspended in hydrobromic acid (200 mL, 48% aqueous solution) and cooled to -15 °C. The reaction was carried out in aqueous solution of sodium nitrite (100 mL). Bromine (95 g, 0.59 mol) was slowly added dropwise, followed by an aqueous solution (100 mL) of sodium nitrite (69 g, 1 mol), while keeping the temperature of the reaction mixture below -15 °C. The reaction mixture was then cooled to -15 °C. After completion of the dropwise addition, the cooling bath was removed and the reaction mixture was stirred for 3 hours at room temperature. The reaction was cooled again to -15 °C and quenched with an aqueous solution (500 mL) of potassium hydroxide (112 g, 2 mol). After removing the cooling bath, stirring was continued for 1.5 hours. The product was extracted with ethyl acetate (3 x 300 mL), the organic phases were combined, washed sequentially with water (2 x 200 mL), saturated aqueous sodium bicarbonate (200 mL), dried over sodium sulfate and concentrated to dryness under reduced pressure. The oily residue was dissolved in chloroform (100 mL), filtered through a silica gel pad and washed with chloroform. The filtrates were combined and evaporated under reduced pressure to give the light yellow solid product 49 (87 g, 94%) with a melting point of 38-40 °C (literature value: 41-42 °C). The structure of the product was confirmed by 1H NMR (300 MHz, CDCl3) δ 8.22 (d, J = 2.4 Hz, 1H), 7.61 (d, J = 2.4 Hz, 1H), 2.33 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 148.29, 143.05, 141.15, 137.15, 119.68, 22.06 Confirmed.

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